From the Pediatric Infectious Disease, Children's Hospital of Orange County, Orange, California.
Division of Infectious Diseases, Rady Children's Hospital, San Diego, California.
Pediatr Infect Dis J. 2018 Sep;37(9):893-900. doi: 10.1097/INF.0000000000001926.
Staphylococcus aureus, including community-associated methicillin-resistant S. aureus, is an important cause of pediatric bacteremia. Daptomycin is a well-established treatment option for Gram-positive bacteremia in adults, but its safety and efficacy in children require confirmation.
This was a randomized (2:1), evaluator-blinded, multicenter, phase 4 clinical trial comparing intravenous daptomycin with standard-of-care (SOC) for treatment of S. aureus bacteremia in 1- to 17-year-old patients (Clinicaltrials.gov: NCT01728376). Total treatment duration (intravenous followed by oral step-down therapy) was 5-42 days. Daptomycin was dosed once daily by patient age: 12-17 years, 7 mg/kg; 7-11 years, 9 mg/kg and 1-6 years, 12 mg/kg. The primary objective was to evaluate daptomycin safety in children who received ≥1 dose; secondary objectives included comparing daptomycin efficacy with SOC (the trial was not designed to confirm noninferiority) and pharmacokinetic analysis.
Fifty-five children were randomized to daptomycin and 27 to SOC (primarily vancomycin or cefazolin); 90% had S. aureus. In both groups, 15% of patients had drug-related adverse events, primarily diarrhea (4% daptomycin, 8% SOC) and increased creatine phosphokinase (4% daptomycin, 0% SOC). Clinical success (blinded evaluator-assessed complete/partial resolution of bacteremia signs and symptoms 7-14 days after end-of-treatment) rates were similar for daptomycin (88%) and SOC (77%; 95% confidence interval for difference: -9% to 31%). Daptomycin plasma levels across age groups were comparable with those in adults receiving daptomycin at 6 mg/kg.
Once-daily, age-appropriate daptomycin was well tolerated in children with staphylococcal bacteremia; efficacy was comparable with SOC. Daptomycin in age-adjusted doses is a safe treatment alternative in this setting.
金黄色葡萄球菌（包括社区获得性耐甲氧西林金黄色葡萄球菌）是小儿菌血症的重要病因。达托霉素是治疗成人革兰阳性菌菌血症的一种成熟治疗选择，但该药在儿童中的安全性和疗效尚需确认。
这是一项比较达托霉素与标准治疗（SOC）在 1 至 17 岁金黄色葡萄球菌菌血症患儿中的疗效和安全性的随机（2:1）、设盲、多中心、4 期临床试验（Clinicaltrials.gov：NCT01728376）。总治疗时间（静脉给药后继以口服降阶梯治疗）为 5-42 天。根据患儿年龄给予达托霉素：12-17 岁者，7mg/kg；7-11 岁者，9mg/kg；1-6 岁者，12mg/kg，每日 1 次给药。主要研究终点为评估至少接受 1 剂治疗的患儿的达托霉素安全性；次要研究终点包括比较达托霉素与 SOC 的疗效（该试验并非旨在确认非劣效性）和药代动力学分析。
55 例患儿随机分至达托霉素组，27 例患儿分至 SOC 组（主要为万古霉素或头孢唑林）；90%的患儿为金黄色葡萄球菌感染。两组中，各有 15%的患儿发生与药物相关的不良事件，主要为腹泻（达托霉素组 4%，SOC 组 8%）和肌酸磷酸激酶升高（达托霉素组 4%，SOC 组 0%）。达托霉素组和 SOC 组的临床治愈率（治疗结束后 7-14 天血培养完全/部分清除的盲法评估者评估结果）相似，分别为 88%和 77%（差异 95%置信区间：-9%至 31%）。达托霉素在各年龄组的血浆水平与接受达托霉素 6mg/kg 治疗的成年患者相当。
在金黄色葡萄球菌菌血症患儿中，每日 1 次、按年龄调整剂量的达托霉素耐受良好；疗效与 SOC 相当。在该治疗环境中，达托霉素是一种安全的治疗选择。
